Conservative treatments like ocular massage may be 'futile'

Action Points

Note that this meta-analysis suggests that fibrinolytic therapy, particularly if given within the first 4.5 hours of symptoms, may be the best option for patients with central retinal artery occlusion.

Be aware that the findings were drive by data from observational studies.

Giving systemic fibrinolysis early enough may stave off blindness due to a central retinal artery occlusion (CRAO), researchers reported.

In a meta-analysis, recovery rates were significantly higher with systemic clot-busting drugs than with no treatment or with conservative treatment (31.3% versus 17.7% and 7.4%), reported Matthew Schrag, MD, of Yale University, and colleagues.

The findings suggest that a clinical trial of systemic fibrinolysis in CRAO is in order, and that current standard conservative treatments may be "futile," they wrote online in JAMA Neurology.

"We found no convincing evidence from the literature that any conservative treatment modality (specifically, ocular massage, hemodilution, and/or anterior chamber paracentesis) is effective, and the results from this meta-analysis suggest that these modalities may be harmful," they explained. "The recovery rate in patients treated in this fashion was less than half that of patients receiving no treatment."

CRAO is an ophthalmologic emergency that can result in blindness in many patients. It results from thrombosis or an embolism that leads to ischemia of the retina and optic nerve head, and these clots are thought to arise from atherosclerotic plaques, carotid stenosis, inflammatory vascular disease, or cardiac abnormalities.

Ophthalmologists have some treatment tools at their disposal, including sublingual isosorbide dinitrate, systemic pentoxyfylline, inhalation of 10% carbon dioxide, hyperbaric oxygen, ocular massage, and corticosteroids. But none has ever been shown to be more effective than placebo.

There are also fibrinolytic treatments, ranging from local and systemic to intra-arterial delivery, but in the EAGLE trial, intra-arterial delivery didn't improve visual outcomes. However, patients in this trial were treated between 4.5 and 12 hours after their symptoms began.

Schrag and colleagues said fibrinolysis may need to start earlier, and since systemic therapies are widely used and have a good safety record, they may be the optimal means of delivery.

They found that recovery rates were significantly higher with systemic clot-busting drugs than with no treatment or with conservative treatment (P<0.001 for each comparison).

Indeed, conservative treatments caused more harm than no treatment, with a number needed to harm of 10.

"This multimodal treatment may reflect a typical clinical approach to this disease that, based on this evidence, should be discouraged," they wrote.

Time was critical when it came to giving fibrinolytic drugs: if given within the first 4.5 hours of symptom onset, there was a 50% recovery rate. This translated to a nearly five-fold increased likelihood of recovery compared with no treatment (OR 4.7, 95% CI 2.3 to 9.6, P<0.001).

The absolute risk reduction was 32.3%, with a number needed to treat of four, Schrag and colleagues added.

If clot-busting drugs were given after 4.5 hours of symptom onset, however, there was no difference in recovery rates compared with no treatment.

Serious hemorrhagic events occurred in 3.4% of patients on systemic fibrinolysis, translating to a number needed to harm of 30. Most of the problems were tied to streptokinase as all five of the serious hemorrhagic events occurred in those on this drug. Four of them were fatal, including three fatal intracerebral hemorrhage and one fatal hemorrhage from the liver.

There were no hemorrhages with tPA or urokinase.

In a subanalysis of patients given tPA only, patients had the best results when it was given within 4.5 hours. Eight of 13 patients recovered if they were treated within that time (P<0.001) compared with only four of 23 who recovered when they were treated 4.5 to 12 hours after symptom onset.

Although they warned that their study was limited by its retrospective and nonrandomized nature, as well as the variability in specific treatment procedures between and within studies, Schrag and colleagues emphasized that there needs to be a clinical trial of early systemic fibrinolytic therapy for CRAO.

"Because of the successful application of systemic fibrinolysis in the setting of acute stroke and because of the similarities between CRAO and stroke, consideration of a similar treatment in acute CRAO is logical," they wrote. "However, differences in the vascular anatomy and metabolic characteristics of the retina preclude direct extrapolation from the stroke literature."

Schrag and co-authors disclosed no relevant relationships with industry.

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